The coronary stent market was reported to be $8.8 billion in 2015 and is expected to grow. An increase in cardiovascular disorders is a primary reason for increasing demand for coronary stents.
Various types of stents are currently available; including bare-metal stents (BMS), bio-absorbable stents, coated stents, drug-eluting stents (DES), and dual-therapy stents. BMS have been observed to cause late-stent thrombosis (blood clots) and in-stent restenosis, which can lead to long-term endothelial dysfunction and/or a chronic inflammation. In-stent restenosis occurs between 3 to 6 months after implantation, whereas late-stent thrombosis occurs between 1 and 12 months after implantation. Although the rate of restenosis decreased initially with DES, once the drug is eluted, similar problems associated with BMS may still occur.
Specifically, the formation of blood clots on a stent's surface in the coronary artery can block or obstruct blood flow, as well as cause serious complications if the clots move to a crucial part of the circulatory system, such as brain or lungs.
The use of biodegradable polymeric stents has the advantage of reducing late stent thrombosis, secondary surgeries, and medical cost for post-percutaneous coronary intervention (PCI) therapy. Polymer stents, however, lack the mechanical properties similar to their permanent metallic counterparts and may lead to increased inflammatory response, neointimal proliferation, and/or extensive cell infiltration.
When in contact with vascular blood flow, the alloys currently used in biocompatible implants are prone to formation of thrombi. The composition of the bulk materials (e.g., alloys) and their surface treatment directly affect surface characteristics responsible for the biocompatibility of the implant or device that employs such materials. These surface characteristics can be, for example, surface composition, roughness, wettability, surface free energy (SFE), and surface morphology.
Specifically, according to Sawyer et al. thrombosis is initiated by an electron transfer process between the surface of a biomaterial and fibrinogen in the blood, leading to a clotting cascade at anodic sites. In the case of cardiovascular stents, thrombogenicity can depend on the stent material's intrinsic properties such as, for example, corrosion resistance, hemocompatibility, and mechanical integrity. Furthermore, extrinsic properties of a stent, such as dimensions, drug and/or polymer coatings, placement with respect to the vessel wall, which imposes specific flow disruptions (e.g., stagnation and recirculation), can also affect the stent's thrombogenicity.
Antithrombogenic properties, or properties responsible for inhibiting the formation of thrombus, are therefore desirable for implants placed in contact with vascular blood before a proper endothelial layer can form at the surface of the stents. Absent any antithrombogenic treatment, deposition of platelets and subsequent formation of thrombus due to exposure to various blood proteins such as fibrinogen, fibronectin, vitronectin, immunoglobulin, and von Willebrand factor (vWF) will quickly ensue.
As a result, it remains a challenge to design a biocompatible and hemocompatible material capable of enhancing the anti-thrombogenicity of stents while retaining advantageous properties of metallic stents.